Synchronized analyte testing system

ABSTRACT

An analyte detection system is provided with calibration information uniquely specific to the set of test strips to which the sample is to be applied. The calibration information may be stored in permanent memory of the testing device, such that the device is discarded after use of all the test strips in a kit, or it may be stored in a calibration chip accompanying the set of test strips and distributed therewith, thereby enabling re-use of the testing device with a different set of test strips and associated calibration chip.

This application is a continuation, of application Ser. No. 09/228,814,filed Jan. 11, 1999 which is now U.S. Pat. No. 6,106,780, which is acontinuation of Ser. No. 08/960,866 filed Oct. 30, 1997 now U.S. Pat.No. 5,872,713 which claims priority of Ser. No. 60/029,201 filed Oct.30, 1996.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to detection devices for determining thepresence or concentration of analytes or biological agents in a sample,and more particularly, to systems using testing instruments to measureanalyte activity on test strips impregnated with appropriate reagents.

2. Description of Related Art

The need for simple methods to determine the chemical and biologicalconstituents in bodily fluids has increased as point of care testing hasgained in popularity. A common application is the self monitoring ofblood glucose concentrations by patients with diabetes. These patientsfrequently administer insulin or take other therapeutic actions based onthe test results. As testing is generally recommended multiple timesdaily and may occur in any setting, an easy to use and relativelyinexpensive method to accomplish this task is required. The costs oftesting are significant to many diabetic patients, especially elderlypatients with fixed incomes and those who are not reimbursed by healthinsurance plans.

In addition to chronic disease monitoring, there are other applicationswhere simple, low cost testing at the point of care may be desired. Forexample, many practitioners believe that certain medications could beadministered much more effectively, both from a medical outcomes andfrom a cost perspective, if the circulating level of such medicationscould be monitored during the course of treatment. Generally, if thelevel of an analyte or biological agent is important enough, the patientneeds to go to a clinic or laboratory and submit to a venipuncture so atest may be run on an expensive clinical instrument. The ability toinexpensively monitor the patient either in the doctor's office or athome could lead to improved outcomes. Given the current pressures onimproving the cost effectiveness of health care, inexpensive, easy touse alternatives to expensive test methods would be welcomed.

The National Institutes of Health conducted a large scale study toevaluate the benefit of long term tight control of the blood glucose forthe diabetic patient. The study, known as the DCCT, proved that longterm tight control of the blood glucose levels in patients had a directrelationship to the health of the patient. One way for the medicalprofession to monitor the control of a patient is for the patient to usea blood glucose monitoring system which has a memory unit to record theblood glucose level and other data such as date and time.

Many diabetics currently use a test method described in U.S. Pat. No.5,304,468 to Phillips et al. This system is comprised of an electronicmeter and a disposable reagent strip. The meter reads the color changeof the strip which correlates to the concentration of the analyte in thesample applied to the strip. The meter is an expensive and complexinstrument which uses multiple light sources or detectors to isolate thereagent color change from the sample color. The user must select thecalibration code for the meter to match the calibration code of the teststrips. In this way, the meter accommodates a wide range of test stripperformance values.

U.S. Pat. No. 4,637,403 to Garcia et al. describes an integrated systemwhich provides a method by which the patient lances the finger to get asample of blood which is then used by the device to read the quantity ofanalyte in the sample. This system uses a complex reflectance system toread the analyte level in the sample.

U.S. Pat. No. 5,279,294 to Anderson et al. describes a hand held shirtpocket device for quantitative measurement of glucose or analytes inbiological fluids. The device has a sophisticated electronics system anda sampling system integrated into one device to determine the quantityof analyte in a bodily fluid sample

U.S. No. Pat. 5,515,170 to Matzinger et al. describes the difficultiesof keeping a strip holder and optics system clean and the need topresent the test strip in the proper perspective to the optics.

European Patent Specification 0 351 891 B1 Hill et al. describes anelectrochemical system and electrodes which are suitable for the invitro determination of blood glucose levels. The system requires the useof expensive electrodes and a sophisticated reader to determine bloodglucose levels.

U.S. Pat. No. 4,994,167 to Shults et al. describes a measuring devicefor determining the presence and amount of a substance in a biologicalfluid using electrochemical methods. This system requires a complexinstrument and method for the patient to determine the quantitativeresult.

U.S. Pat. No. 5,580,794 to Allen et al. describes a single usedisposable measuring device for determining the presence and amount of asubstance in a biological fluid using reflectance methods. This systemutilizes an optics and electronics package which are mated in a singleplane.

Single use disposable devices have been designed for the analysis ofanalytes in bodily fluids. U.S. Pat. No 3,298,789 to Mast describes asystem in which whole blood is applied to a reagent strip. After aprecise, user-timed interval, the blood must be wiped off by the user.An enzyme system reacts with the glucose present in the sample to createa color change which is proportional to the amount of glucose in thesample. The strip may be read visually, by comparing to a printed colorintensity scale, or in an electronic instrument.

U.S. Pat. No. 5,418,142 to Kiser et al. describes a single use devicewhich does not require blood removal or color matching. The amount ofanalyte present in the sample is read in a semiquantitative fashion.

U.S. Pat. No. 5,451,350 to Macho et al. describes a single use systemfor the determination of an analyte in a biological sample.

U.S. Pat. 5,522,255 to Neel et al. describes a fluid dose, flow andcoagulation sensor for a medical instrument which uses a non-volatileelectronic calibration device in the system to check the calibration ofthe reagent strip.

U.S. Pat. No. 5,053,199 to Keiser et. al. describes an electronicallyreadable information carrier for use with a medical device.

U.S. Pat. No. 5,366,609 to White et. al. describes a biosensing meterwith a pluggable memory key. This device uses a pluggable memory keywhich is used to control the operations of the meter.

U.S. Pat. No. 5,307,263 to Brown describes a modular microprocessorbased health monitoring system designed to collect data from a healthmonitoring test system such as a blood glucose monitoring meter.

Although many improvements have been made, the cost and complexity ofmeasuring analyte levels in biological samples remains a significantissue for patients and for the health care system. Even patients who arecovered for blood glucose monitoring supplies must often purchase themeter and await reimbursement. The need to match the calibration of ameter and the strips or electrodes in use leads to errors in performanceand adds cost and complexity for the manufacturers. The availability ofa low cost, simplified quantitative test system for the periodicmonitoring of constituents of biological fluids, such as glucose inblood, would make testing more accessible to patients and would improvetheir well-being and reduce the cost of their care.

Currently, existing calibration mechanisms require the loading of acalibration chip, calibration strip, inputting of a calibration code oruse of a machine readable mechanism on the strip to modify the reactioninterpretation of the meters. These methods can result in errors inreading of the analyte being tested for by using either the wrongcalibration device with a lot of strips or entering the wrongcalibration code for the lot of strips.

In addition, a system which requires a smaller fluid sample would beattractive to many patients. There has been a trend toward smallersample sizes, but most devices still require about 10 μL of blood. Manypatients have difficulty routinely applying an adequate sample to thestrips or electrodes. Inadequate sampling can cause erroneous results ormay require that the user discard an expensive test strip and repeat thesample application procedure.

An additional issue is the use of out of date test strips with themeter. Currently the expiration date and expiration period after openingis printed on the container for the test strips. This presents a problemfor the patient if he or she does not observe the dating information onthe container. The strips can result in an error in the reading whichcan cause false response/treatment by the patient.

SUMMARY OF THE INVENTION

The invention overcomes the deficiencies of the prior art by providing alow cost testing instrument and single use test strips capable ofreading small sample sizes, e.g. 3 μL, and determining the amount of ananalyte in the small sample. The low cost nature of the testinginstrument permits the packaging of the testing instrument and teststrips together in a package, creating a synchronized system which maybe used to perform a specific number of tests. The testing instrument isprovided at no extra cost to the user, who benefits from having a freshdevice with each new package of test strips purchased. This eliminatesthe need for the patient to make an investment in test equipment tomonitor a specific condition or therapy.

In an alternate configuration, the device may be provided as part of astarter package including a sampling device and test strips. Replacementtest strips could be purchased separately without the device or samplerif longer testing instrument life is preferable. For example, the desireto include additional features such as data management capabilitiescould add cost which would favor a longer useful life for the testinginstrument.

The testing instrument incorporates a molded lens optic systemconsisting of one or more channels and a simple electronics packageconsisting of light emitting diodes (LEDs), analog to digital conversionelectronics, a processor unit, Read Only Memory and a digital displaysystem. The testing instrument case has a positioning system whichinterfaces with the test strip to create positive location and alignmentfor the reagent test pad within the strip and the optics.

The applied bodily fluid reacts with the reagents impregnated in thetest pad within the test strip and the resulting color change is read bythe optics system. The signal is converted and displayed on the digitalreadout as the concentration of the analyte in the sample.

An advantageous feature in accordance with the invention is the use of asmall sample sizes, e.g., about 3 μL, which is a fraction of the volumerequired for most blood glucose tests and could be more readily obtainedby patients.

Another advantageous feature in accordance with the invention is theprovision of a simple low cost testing instrument and a complimentaryreagent test strip.

Another advantageous feature in accordance to the invention is the useof reagent test strips that are calibrated to the testing instrumentand/or an intelligent calibration device which may each be one-timereadable mechanisms, eliminating the potential problems of re-use of thecalibration device with the wrong set of test strips.

Another advantageous feature in accordance with the invention is atesting instrument which is precalibrated or synchronized to the lot ofreagents test strips with which it is supplied, eliminating the need forthe user to match or enter calibration information.

Another advantageous feature in accordance with the invention is asystem which is designed for a predetermined number of test results,minimizing upkeep such as cleaning or battery replacement.

Another advantageous feature in accordance with the invention is theelimination of the need for a separate test strip holder, simplifyingthe interface of the disposable portion of the test system with there-usable testing instrument.

Another advantageous feature in accordance with the invention is theelimination of the need for a patient to calibrate the meter for thetest strips or keep track of expiration dating by placing theinformation on a single use calibration chip.

BRIEF DESCRIPTION OF THE DRAWINGS

Many advantages of the present invention will be apparent to thoseskilled in the art with a reading of this specification in conjunctionwith the attached drawings, wherein like reference numerals are appliedto like elements and wherein:

FIG. 1 is a perspective view of one embodiment of a test strip comprisedof a test pad and holder for body fluid analysis.

FIG. 2 is a perspective view of one embodiment of the testing instrumenthaving a test pad holder.

FIG. 3 illustrates the testing instrument and a test strip incommunication with the test strip.

FIG. 4 is a block diagram of the testing instrument electronics andoptics for reading the test strip.

FIGS. 5A and 5B illustrate a method of confirming the wetting of thetest pad and contact to start the timing of the testing instrument.

FIG. 6 shows a kit of the system including testing instrument and teststrips.

FIG. 7 shows a kit of the system including testing instrument, teststrips and sampling devices.

FIG. 8 shows the use of two detectors and two emitters in an opticssystem.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

FIG. 1 is a perspective view showing the test strip 11 for use with thedetection device in accordance with the invention, the test strip 11comprising a test pad 12 and holder 13 for analysis of bodily fluid 16.The test strip 11 provides a handle 14 for the patient to hold the strip11. The handle operates as a wick to transfer the bodily fluid 16 to thetest pad 12 and is provided with a channel 10 for this purpose. The testpad 12 may be formed from bibulous matrix which has been impregnatedwith a reagent system comprised of enzymes, indicators and bloodseparation agents.

Test strip 11 is provided with an alignment mechanism which may compriserecess 17 and projection 18 disposed on bottom portion 15 of the teststrip 11. These operate to insure positive location and orientation ofthe test strip 11 with respect to the testing instrument 21 of theinvention by engaging corresponding portions of the testing instrumentas explained below. Of course it is contemplated that other test stripconfigurations can be used with the system of the invention withoutpatentable departure from the spirit and scope of the invention.

FIG. 2 is a perspective view of testing instrument 21 which is used toread test strip 11 in accordance with the invention. The testinginstrument 21 has a housing 22 which is provided with optics view window23 and a docking portion 37 for mating with alignment recess 17 andprojection 18 of test strip 11. Docking portion 37 may comprise a slot20 disposed in a retaining clip 19 which operates to guide handle 14 oftest strip 11 into position, along with a recess 24 to mate withprojection 18 of the test strip 11. Proper alignment for accuratereading is thereby insured, as illustrated in FIG. 3, which shows thetesting instrument 21 in operational position in communication with thetest strip 11.

Testing instrument 21 is also provided with a sensor 45 for measuringthe analyte concentration in sample 16, along with a display 49 fordisplaying the result. The sensor 45 may be optical in nature, and asshown in FIG. 8, may comprise paired light emitter and detector devices.Specifically, an LED emitter 50 and A photodetector 51 measure reflectedlight from the sample-containing test pad 12. This reflected light isproportional to the amount of analyte in the sample as manifested by theextent of reaction of the sample/analyte with the reagent on the testpad 12. Ambient light is blocked by a design of test strip 11 andtesting instrument 21 which minimizes error induced by ambient lightcorrupting the reflectance reading. Such a design may includeappropriately limiting the size of view window 23 while selectingsufficiently opaque materials to form the material of the housing 22from which view window 23 is formed, thus operating to effectively forman optical shield.

Insuring proper alignment in accordance with the invention also servesto minimize ambient light corruption.

In accordance with the invention, numerous optical schemes may beemployed, including use of transmitted rather than reflected light,multiple LED/detector pairs and various arrangements thereof. It is alsocontemplated that various light source:light detector ratios maybe used,departing from the one-to-one correspondence disclosed.

In accordance with the invention, an LED 53 is also provided andcorresponds with a photodetector 52. The photodetectors 51 and 52 may beselected to operate at different light intensity levels, such that lightbelow or at a predetermined intensity threshold is measured by onephotodetector, while light above the threshold is measured by the otherphotodetector. Alternatively, one detector can be used to measurereflectance of a particular color component, while the other measuresthe reflectance of a different color component, or one detector canmeasure overall light intensity while the other measures a colorcomponent. Also, a reference detector (not shown) could be employed tocompensate for the deterioration of the LED intensity over time. Inalternative arrangement, the measurement from one detector can be usedto provide a compensation for hematocrit level or oxygen content of theblood. One of ordinary skill in the art will realize many modificationsand remain within the purview of the invention.

An optical arrangement in accordance with the invention is furtherprovided with a molded plastic lens system 48 to focus light to and fromthe sample on the test pad 12. Such an arrangement provides thecapability of focusing the light to and from a small reaction area,which reduces the size of the test pad 12 and the amount of samplerequired to effect the testing procedure. Advantages thus realizedinclude reduction in size/cost of the matrix employed and quantity ofexpensive reagents required.

The optics of the invention may include appropriate optical filtering tooptimize measurement, or electronic filtering and masking techniques maybe employed to improve signal-to-noise levels. An optical filteringscheme of the invention, when blood analysis is to be performed,involves the use of existing membrane materials with a blocking fillerto create an opaque membrane which blocks interference from red bloodcells and can assist in the separation of red blood cells fromrelatively clear fluid.

Another optical configuration uses multiple LED and photodetector pairs.A first pair is used to achieve the primary analyte determination. Asecond pair is used to monitor test initiation and to quantifyhemoglobin and hematocrit. Subsequent pairs are used to monitor nativecolor effects of lympic and icteric samples. Additional optical pairsare used in association with added chemical components in the strip forspecific determination of possible interference factors such as pH,specific gravity, etc. as well as for specific determination ofadditional analytes such as cholesterol, triglycerides, etc. Suchanalysis, possibly using different wavelengths, provides significantbenefits to overcoming interfering effects from the sample and theenvironment. By selecting wavelength pairs which are tuned to detectcomponents of the test, it is possible to isolate and quantify theanalyte, hematocrit and red blood cell contributions in a testing event.In accordance with the invention, interference from the environment isminimized by separating its effects and monitoring each oneindependently using multiple optical systems. Through detection andquantification, the individual contribution to the measurement can besubtracted from the analyte measurement. With the ever decreasing costof computing power, and a unique of constructing multiple opticalsystems at very low cost, the approach of the invention is readilyapplicable to home diagnostic use.

The test strip 11 is comprised of a test pad 12 situated in a test padholder 13. This holder provides a means for accurately positioning thetest pad 12 with respect to the sensor 45 in addition to providing ameans. for blocking ambient light from effecting the analysis. The testpad 12 is impregnated with the appropriate chemistry to permit acolormetric analysis of the analyte being tested and may thereforeprovide a stable absorbent substrate.

The test strip 11 of this invention differs from current test strips inmultiple ways. For current test strips, the nonporous support provides ahandle for the patient [U.S. Pat. No. 5,526,120 Jina et al.], and/or ameans of aligning the test strip in a strip holder [U.S. Pat. No.5,515,170 Matzinger et al.] The test strip of this invention doesprovide a support for the test pad. The strip positively seats on thetesting instrument, assuring proper alignment. It also seals the opticsarea from ambient light and blood contamination. Thus it provides all ofthe functionality of a test strip and test strip holder of aconventional reflectance system. The test strip provides additionalbenefits in being removed after each test, facilitating easy access tothe optics area for cleaning if required. With this combination part,the overall cost of the system is further reduced. When inserted intothe detection device 21, the test strip 11 contacts complete a circuitwhich turns the device on. The device is turned off upon removal of thetest strip. This eliminates a need for a separate on/off circuit orpatient action to turn the testing instrument on or off.

The signal producing system impregnated in the test pad matrix can beformed from different indicator systems such as3-methyl-2-benzothiazolinone hydrazone (MBTH) and8-anilino-1-naphthalenessulfonate(ANS) [U.S. Pat. No. 5,453,360 Yu],MBTH and 3-dimethylaminobenzoic acid (DMAB) [U.S. Pat. No. 5,049,487Phillips et al.], 3-methyl-2-benzothiazolinone-hydrazone-sulfonatesodium salt (MBTH-SO₄) and ANS [U.S. patent application 08/628,794Douglas et al.], MBTH-SO₄ and N-(3-sulfopropyl)aniline (HALPS) [U.S Pat.No. 4,396,714 Maeda et al. and U.S. patent application 08/628,794Douglas et al.], MBTH-SO₄ and N-Ethyl-N-(3-sulfopropyl)aniline ALPS[U.S. Pat. No. 4,396,714 Maeda et. al. and U.S. patent application08/628,794 Douglas et al.]. One skilled in the art could devise analternate indicator system. The oxidase enzyme system contained in thereagent pad produces hydrogen peroxide which is used to convert theindicator with the assistance of peroxidase which acts as the catalyst.

In the most preferred embodiment the reagents are impregnated into aporous membrane by submerging the dry membrane into a reagent dip.Excess fluid is wiped from the membrane surface and the membrane isgently dried in an oven. At this point, subsequent dipping and dryingcan be conducted. A preferred embodiment for a two dip process is:

MBTH-SO₄ & ALPS Formulation

Final Concentrations A Dip In Citrate Buffer, pH 7 0.1M stock A Dip EDTA0.08% mannitol 0.19% Gantrez-S95 0.53% Klucel 99-EF 20 uM Crotein-SPA7.45% enzyme reagents Glucose Oxidase 0.92% Peroxidase 0.54% B Dip In70% Ethanol MBTH-SO₄ 0.66% ALPS 2.00% SOS 0.20%

The assembly of a system kit comprised of a testing instrument and aspecific number of synchronized test. strips for the testing of aspecific analyte can provide a simple, cost effective test method andprocedure.

FIG. 4 is a block diagram showing the processing operation of theinvention. Testing instrument 21 comprises a microprocessor 41 whichcontrols the operation of the testing instrument 21. The testing intent21 is activated by a switching mechanism which may comprise a mechanicalON button 34 and contacts 30-33 which close an appropriate circuit whenthe button 34 is depressed. Closing of this circuit triggers operationof the device by notifying the microprocessor 41 that a measurementreading of a positioned test strip 11 is to be performed. The test stripmay be one of a number of. test strips in the set, and a counter keepstrack of these. Alternatively, the circuit may be closed via a fluidconnection using the test sample, with the contacts 30 and 31 operatingas probes provided for making contact with the test pad 12 of the teststrip 11 to thereby activate the testing instrument 21 upon detection ofthe sample on the appropriately positioned test strip 11.

FIGS. 5A and 5B illustrate a method of confirming the wetting of thetest pad 12 to start the testing instrument 21. The test strip 11 ofFIG. 5B is configured to have contacts 54 and 55 disposed on the testpad 12 thereof. The contacts 54 and 55 are spaced apart a finitedistance, and are only in electrical communication by virtue of a fluidcontact formed by the sample. The sample 16 is applied to the test strip11, wetting the test pad 12 and contacts 54 and 55. The contacts 54 and55 are in communication with contacts 30 and 31 on testing instrument 21so when wetted this completes a circuit which starts the testinginstrument 21 and begins the analysis of the sample. Of course, otheractivation schemes can be utilized by the invention. Two such schemesmay be optical or mechanical detection of the test strip 11 in dockingportion 37.

Following activation, measurement of the reaction of the sample with thereagent on the test strip 11 is effected using the optical sensor 45. Ofcourse, the sensor itself need not be of the optical type—otherexpedients, such as electrochemical detection, e.g., fall within thepurview of the invention. The microprocessor derives an electricalsignal from the sensor 45, comprising electro-optical devices 50 and 52,and processes it to generate a detection signal indicative of analyteconcentration in the tested sample. An ASIC 43 (application-specificintegrated circuit) and a memory, such as RAM (random access memory) 42or a ROM (read only memory) may be used in conjunction with themicroprocessor 41, while the results of the measurement may then bedisplayed using LCD display 49. The results may alternatively be storedin RAM 42 for subsequent viewing or processing. The subsequentprocessing may be performed using the measuring instrument 21 itself, orusing other devices to which the measurement results can be downloaded.One possibility in accordance with the invention is a modem link with aremote processing unit, using, e.g., telephone lines. The informationmay also be downloaded for storage at an internet location or electronicbulletin board for subsequent retrieval and processing or review bymedical professionals.

One feature in accordance with the invention is the use of a calibrationchip 40 as shown in FIG. 4. The calibration chip is detachablyconnectable to the testing instrument 21 for electronic communicationwith the microprocessor 41. It may be any form of volatile ornon-volatile memory including single use microprocessors, EPROMs orEEPROMs thus forming an intelligent chip permitting intelligent datatransfer between the chip and the testing instrument 21. Calibrationchip 40 contains calibration information which is uniquely specific tothe reagent provided with a particular set of test strips 11 distributedwith the calibration chip. In this way, lot differences in the reagentcan be compensated for using the required information andsophistication, while at the same time obviating the need for the userto enter or contribute to this information. This minimizes error andgreatly facilitates use and accuracy of the testing instrument 21 of theinvention.

The color formed after applying the bodily fluid to the reagent test padis proportional to the amount of analyte in the applied sample 16. Thetesting instrument 21, via sensor 45 and microprocessor 41, measures thechange in reflectance due to the development of the specific colorgenerated by the reagent on the test strip 11. This is either used asthe input to a function which relates reflectance to analyte level or toa table which correlates reflectance value to analyte level. Thefunction or the table must be stored within the system for it to produceand display, on display 49, a reading of the analyte level in the sample16. While most meters in use today employ functions to convertreflectance readings to analyte concentration, this approach requiresthat the function be stable and well understood. The use of a look uptable permits the storage of specific values for reflectance and theircorresponding analyte levels. The testing instrument uses this table andinterpolates between the table values to give relatively accuratereadings. This is achievable in a system such as that described by thisinvention as the table can quickly be generated for each reagent lotproduced.

In the preferred embodiment, calibration is based on the responseproduced by a specific lot of test strips. In this manner, there is noneed to presort and test the LEDs 50 and 53, significantly reducing thecost of the sensor 45. In addition, this calibration step duringmanufacture allows the device to compensate for a wide area of variablesnormally found in reflectance systems. The specific calibration data forthe test strips 11 shipped with the testing instrument can be stored inthe unit's read only memory (not shown). Alternatively, a master stripcan be provided for setting the calibration information for that lot ofstrips and the master strip can be distributed therewith. A counter maybe provided to limit the testing instrument 21 to performing only aspecific number of tests which correlates to the quantity of test strips11 shipped with the device. Other limitations can be built-in, such asexpiration date information pertaining to the specific lot of teststrips 11 with this information being contained in the measuringinstrument's ROM or in the calibration chip 40 or in the master strip.

A more traditional approach to calibration may alternatively be taken. Acalibration algorithm, with several settings if necessary, could beprogrammed into the system if the testing instrument has a longerprojected life and is to be used with multiple sets of test strips.

If a microprocessor is used for the calibration chip, the chip may beprovided with its own power source for memory information retention. Toprevent re-use when an EPROM or other memory device is used as thecalibration chip, an optional mechanical latch 44 which would eliminatethe ability to engage the calibration chip into the testing instrument21 a second time. Similarly, when a microprocessor or EEPROM or othermemory device is used, the calibration chip 40 may have its dataoverwritten or an indicator bit thereof be written by the microprocessor41 following its use to prevent reuse. The calibration informationstored in the calibration chip 40 is thus downloaded to the processormemory 42, and the calibration chip is disabled, preventing re-usethereof. The calibration information contains the permitted number oftest strip analyses to be performed, the number corresponding to thenumber of test strips provided with the kit. The calibration chip itselfcan then be disposed of.

Alternatively, a counter (not shown) may be provided in the calibrationchip, the counter being decremented each time the chip is read. In thismanner, only a limited number of readings, corresponding to the numberof test strips 11 provided with the calibration chip 40 can beperformed. It is also contemplated that calibration information providesan expiration date preventing use of the calibration chip and/orassociated strips thereafter, or a duration can be measured after whichuse of the chip and/or associated strips is precluded. The duration canbe commenced from time of opening a package in which the kit isprovided, or from any other similar time, such as the time of first useof the calibration chip 40. The ordinarily skilled artisan will findnumerous variations can be effected without departure from the spiritand scope of the invention.

The patient uses the system by removing the testing instrument from thepackaging and placing it on a firm surface. The next step is to remove atest strip and insert it in the testing instrument. Inserting the teststrip activates the unit, eliminating the need for a power on/off buttonor switch. The patient then uses either a sampler 60 (FIG. 7) from thekit or one procured separately to draw a sample of capillary blood. Thekit may optionally be provided with a sampling device 62 as well. Thesample is applied to the test strip, initiating a timing sequence, andthe testing instrument displays the results after an appropriate time.Alternatively, the patient may first apply the blood sample to the teststrip, then insert the strip into the testing instrument to activate thetest cycle and read out of test results.

The subject invention provides improvements over existing technology inuse today in several ways. The preferred embodiment of the inventioneliminates the need for a patient to purchase a costly system to conductroutine testing of body fluids. It also eliminates the existingdependence on the customer to maintain the testing instrument andmonitor/compensate for reagent lot differences. The invention providesthis easy to use format for analytes such as glucose by incorporatingadvanced lens based optics and low cost modern electronics. The use oflens based optics permits the system to focus on small reaction areawhich reduces the size of the test pad. The resulting small test padreduces the cost of the matrix employed and the quantity of expensivereagents needed to conduct an accurate assay using an oxidase andperoxidase chemistry. With a smaller test pad, a smaller sample volumeis adequate. The system conserves the energy used and minimizes theamount of light required by the system to determine the color change.The optics modules are calibrated during the manufacture of the testinginstrument.

An important feature in accordance with the invention is the manufactureand calibration of the testing instrument 21 for use with a specificquantity of test strips 11 which have been matched at the factory. Thislimits the need for calibration codes, and minimizes the maintenancerequired by the patient in the form of cleaning, battery replacement andcalibration code changes. It also improves the system's ability toprovide long term accurate results because a testing instrument issynchronized with only certain test strips. Once they have been used, acomplete new kit is acquired with a testing instrument calibratedspecifically for those test strips. This eliminates much of thecompromise in system performance found in current products which have towork with strips made over a wide range of production conditions andinput states.

The above are exemplary modes of carrying out the invention and are notintended to be limiting. It will be apparent to those skilled in the artthat modifications thereto can be made without departure from the spiritand scope of the invention as set forth by the following claims.

What is claimed is:
 1. A system for detecting the presence of an analytein a sample of biological fluid having a volume on the order of 3 μL,the system comprising: a set of test strips; and a detection devicecomprising a testing instrument having: a housing having a dockingportion for engaging at least one of the test strips; a sensor disposedat least partially in the housing and constructed to generate a signalresponsive to reading the sample; and a processor disposed at leastpartially in the housing and adapted to operate to generate a detectionsignal representative of the presence of the analyte in the sample;wherein the detection device and test strips are constructed such thatthe system is capable of accurately detecting the analyte in the samplehaving a volume on the order of 3 μL.
 2. The system of claim 1, whereinthe processor contains calibration information.
 3. A testing system fordetecting the presence of an analyte in a sample of biological fluids,the system comprising: a plurality of test pads; a testing devicecomprising a housing, a sensor disposed at least partially in the ishousing and adapted to generate a signal responsive to reading thesample, a processor disposed at least partially in the housing andadapted to generate a detecting signal representative of the presence ofthe analyte in the sample, and a permanent memory; and calibrationinformation corresponding to the plurality of test pads stored in thepermanent memory of the testing device.
 4. The system of claim 3,wherein each of the plurality of test pads are contained in a respectivetest strip.
 5. A testing system for detecting the presence of an analytein a sample of biological fluids, the system comprising: a plurality oftest pads; a calibration chip containing calibration informationcorresponding to the plurality of test pads; and a testing devicecomprising a housing, a sensor disposed at least partially in thehousing and adapted to generate a signal responsive to reading thesample, a processor disposed at least partially in the housing andadapted to generate a detecting signal representative of the presence ofthe analyte in the sample and in accordance with the calibrationinformation.
 6. The system of claim 5, wherein each of the plurality oftest pads are contained in a respective test strip.
 7. A system,comprising: a set of test strips; a calibration means corresponding tothe set of test strips and containing calibration information uniquelycharacteristic to the reagent in the set of test strips; and a detectiondevice comprising a testing instrument having a housing; a sensor atleast partially within the housing and constructed to generate a signalresponsive to reading the sample; and a processor at least partiallywithin the housing; wherein the calibration means has means for limitingits use to a predetermined number of times which does not exceed thenumber of test strips in a given set such that the calibration means isdisabled after reading the last test strip in the set.